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Related Concept Videos

Chromatin Packaging02:21

Chromatin Packaging

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Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter? 
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order...
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Chromatin Packaging01:32

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Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
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Exploring chromatin hierarchical organization via Markov State Modelling.

Zhen Wah Tan1, Enrico Guarnera1, Igor N Berezovsky1,2

  • 1Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Matrix, Singapore.

Plos Computational Biology
|January 1, 2019
PubMed
Summary
This summary is machine-generated.

We developed a new computational method using Markov State Modelling to reveal the hierarchical structure of chromosomes from Hi-C data. This approach maps epigenetic information to understand how chromatin organization influences genome function.

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Area of Science:

  • Computational Biology
  • Genomics
  • Structural Biology

Background:

  • Chromatin's three-dimensional structure is crucial for genome regulation and function.
  • Understanding chromosome organization at different scales remains a challenge.

Purpose of the Study:

  • To introduce a novel computational method for analyzing chromatin structural organization.
  • To investigate the hierarchical structure and interactions within and between chromosomes.
  • To link chromatin architecture to genome function through epigenetic data integration.

Main Methods:

  • Markov State Modelling (MSM) of Hi-C interaction data.
  • Analysis of Markov State Model metastability upon annealing to identify hierarchical partitions.
  • Derivation of effective interactions between genomic partitions.
  • Mapping epigenetic and gene expression data onto the derived interaction networks.

Main Results:

  • Identified hierarchical structural partitions within chromosomes, analogous to topologically associating domains and epigenomic compartments.
  • Delineated whole-genome architecture and inter-chromosomal associations.
  • Revealed structure-function relationships by correlating chromatin organization with epigenetic factors and gene expression regulators.
  • Developed a freely available Python package, ChromaWalker, to implement the method.

Conclusions:

  • The proposed MSM-based method provides a robust framework for chromatin structural reconstruction and dynamic modeling.
  • The analysis reveals key insights into genome architecture and its role in regulating gene function.
  • This work lays the foundation for further exploration of chromatin dynamics and genome regulation.